Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “BONE FRACTURES”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

Adaptation of the Skeletal System during Long-duration Spaceflight

This review will highlight evidence from crew members flown on space missions greater than 90 days to suggest that the adaptations of the skeletal system to mechanical unloading may predispose crew members to an accelerated onset of osteoporosis after return to Earth. By definition, osteoporosis is a skeletal disorder - characterized by low bone mineral density and structural deterioration - that reduces the ability of bones to resist fracture under the loading of normal daily activities. Involutional or agerelated osteoporosis is readily recognized as a syndrome afflicting the elderly population because of the insipid and asymptomatic nature of bone loss that does not typically manifest as fractures until after age approximately 60. It is not the thesis of this review to suggest that spaceflight-induced bone loss is similar to bone loss induced by metabolic bone disease; rather this review draws parallels between the rapid and earlier loss in females that occurs with menopause and the rapid bone loss in middle-aged crew members that occurs with spaceflight unloading and how the cumulative effects of spaceflight and ageing could be detrimental, particularly if skeletal effects are totally or partially irreversible. In brief, this report will provide detailed evidence that long-duration crew members, exposed to the weightlessness of space for the typical long-duration (4-6 months) mission on Mir or the International Space Station -- 1. Display bone resorption that is aggressive, that targets normally weight-bearing skeletal sites, that is uncoupled to bone formation and that results in areal BMD deficits that can range between 6-20% of preflight BMD; 2. Display compartment-specific declines in volumetric BMD in the proximal femur (a skeletal site of clinical interest) that significantly reduces its compressive and bending strength and which may account for the loss in hip bone strength (i.e., force to failure); 3. Recover BMD over a post-flight time period that exceeds spaceflight exposure but for which the restoration of whole bone strength remains an open issue and may involve structural alteration; and 4. Display risk factors for bone loss -- such as the negative calcium balance and down-regulated calcium-regulating hormones in response to bone atrophy -- that can be compounded by the constraints of conducting mission operations (inability to provide essential nutrients and vitamins). The full characterization of the skeletal response to mechanical unloading in space is not complete. In particular, countermeasures used to date have been inadequate and it is not yet known whether more appropriate countermeasures can prevent the changes in bone that have been found in previous flights, knowledge gaps related to the effects of prolonged (greater than or equal to 6 months) space exposure and to partial gravity environments are substantial, and longitudinal measurements on crew members after spaceflight are required to assess the full impact on skeletal recovery.

Sibonga, Jean D.↗
NASA NTRS2010

Data Mining Activity for Bone Discipline: Calculating a Factor of Risk for Hip Fracture in Long-Duration Astronauts

The factor-of-risk (Phi), defined as the ratio of applied load to bone strength, is a biomechanical approach to hip fracture risk assessment that may be used to identify subjects who are at increased risk for fracture. The purpose of this project was to calculate the factor of risk in long duration astronauts after return from a mission on the International Space Station (ISS), which is typically 6 months in duration. The load applied to the hip was calculated for a sideways fall from standing height based on the individual height and weight of the astronauts. The soft tissue thickness overlying the greater trochanter was measured from the DXA whole body scans and used to estimate attenuation of the impact force provided by soft tissues overlying the hip. Femoral strength was estimated from femoral areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry (DXA), which were performed between 5-32 days of landing. All long-duration NASA astronauts from Expedition 1 to 18 were included in this study, where repeat flyers were treated as separate subjects. Male astronauts (n=20) had a significantly higher factor of risk for hip fracture Phi than females (n=5), with preflight values of 0.83+/-0.11 and 0.36+/-0.07, respectively, but there was no significant difference between preflight and postflight Phi (Figure 1). Femoral aBMD measurements were not found to be significantly different between men and women. Three men and no women exceeded the theoretical fracture threshold of Phi=1 immediately postflight, indicating that they would likely suffer a hip fracture if they were to experience a sideways fall with impact to the greater trochanter. These data suggest that male astronauts may be at greater risk for hip fracture than women following spaceflight, primarily due to relatively less soft tissue thickness and subsequently greater impact force.

Ellman, R.↗
NASA NTRS1991

Mechanical response tissue analyzer for estimating bone strength

One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

Arnaud, Sara B.↗
DOE OSTI2016

Percutaneous Augmented Peripheral Osteoplasty in Long Bones of Oncologic Patients for Pain Reduction and Prevention of Impeding Pathologic Fracture: The Rebar Concept

PurposeTo evaluate clinical efficacy/safety of augmented peripheral osteoplasty in oncologic patients with long-term follow-up.Materials and MethodsPercutaneous augmented peripheral osteoplasty was performed in 12 patients suffering from symptomatic lesions of long bones. Under extensive local sterility measures, anesthesiology care, and fluoroscopic guidance, direct access to lesion was obtained and coaxially a metallic mesh consisting of 25–50 medical grade stainless steel micro-needles (22 G, 2–6 cm length) was inserted. PMMA for vertebroplasty was finally injected under fluoroscopic control. CT assessed implant position 24-h post-treatment.ResultsClinical evaluation included immediate and delayed follow-up studies of patient’s general condition, NVS pain score, and neurological status. Imaging assessed implant’s long-term stability. Mean follow-up was 16.17 ± 10.93 months (range 2–36 months). Comparing patients’ scores prior (8.33 ± 1.67 NVS units) and post (1.42 ± 1.62 NVS units) augmented peripheral osteoplasty, there was a mean decrease of 6.92 ± 1.51 NVS units. Overall mobility improved in 12/12 patients. No complication was observed.ConclusionPercutaneous augmented peripheral osteoplasty (rebar concept) for symptomatic malignant lesions in long bones seems to be a possible new technique for bone stabilization. This combination seems to provide necessary stability against shearing forces applied in long bones during weight bearing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS1999

Preparing for Mars: the physiologic and medical challenges

As the twentieth century closes, retrospectives cite the Apollo moon missions as one of the important events of the past 100 years. A trip to Mars, however, would be even more challenging and significant. A round-trip Mars journey would require nearly three years away from Earth, a significant leap in complexity compared to the two week long Moon trips or the record-breaking fourteen-month flight on Mir. What would be the physiologic and medical challenges of a Mars flight? Two key areas of physiology present the greatest potential problems--calcium metabolism and radiation exposure. Data from Mir missions show that bone loss continues in space despite an aggressive countermeasure program. Average losses were 0.35% per month, but some load bearing areas lost >1% per month. A 1% loss rate, if it continued unabated for 30 months, could produce osteoporosis. Smaller losses could still increase fracture risk. Some bone loss can be well tolerated, particularly if the bone can be regained after the mission. But the effectiveness of post-flight rehabilitation to restore the density and quality of bone after spaceflight is not well known. Bone loss estimates are based on continuous weightlessness exposure, but this is not a requirement for a Mars trip. Most of the time on a Mars trip will be spent in the 1/3 Earth's gravity environment on Mars, and either intermittent or continuous artificial gravity can be provided for the transit between planets (although at an engineering cost). The dosing of the gravity exposure (e.g. the level and duration), however, has not been established. Radiation protection also requires a balance between engineering cost and human health. Excessive shielding could add billions of dollars to the cost of a mission. Trips in interplanetary space, however, expose the crew to heavy high-energy particles from cosmic rays (HZE particles), which have a high linear energy transfer. This high energy leads to significant biological damage (e.g. chromosomal aberrations, cancer induction). A recent report from the Committee on Space Biology and Medicine notes that only one systematic study of cancer induction from high-energy particles has been conducted (using the mouse Harderian gland). Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data. Other areas of physiology also present problems, such as muscle loss, cardiovascular deconditioning, and vestibular adaptation. Despite all the issues, however, a focussed, aggressive research program that uses the resources of the International Space Station should pave the way for mankind's greatest adventure--a trip to Mars.

STS-90 Shuttle Project↗
DOE OSTI2015

Obtaining of biodegradable polylactide films and fibers filled hydroxyapatite for medical purposes

Relevance of the work is due to the need for new materials that are used in medicine (orthopedics, surgery, dentistry, and others) as a substitute for natural bone tissue injuries, fractures, etc. The aim of presented work is developing of a method of producing biocompatible materials based on polyesters of hydroxycarboxylic acids and calcium phosphate ceramic (hydroxyapatite, HA) with homogeneous distribution of the inorganic component. Bioactive composites based on poly-L-lactide (PL) and hydroxyapatite with homogeneous distribution were prepared. The results of scanning electron microscopy confirm homogeneous distribution of the inorganic filler in the polymer matrix. The positive effect of ultrasound on the homogeneity of the composites was determined. The rate of hydrolysis of composites was evaluated. The rate of hydrolysis of polylactide as an individual substance is 7 times lower than the rate of hydrolysis of the polylactide as a part of the composite. It was found that materials submarines HA composite and do not cause a negative response in the cells of the immune system, while contributing to anti-inflammatory cytokines released by cells.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics: HIP BMD LOSS & FRACTURE RISK MARKERS BY POPULATION-BASED SERUM PROTEOMICS

Accelerated bone loss significantly increases the risk of osteoporosis and fracture. The mechanisms underlying bone loss remain incompletely understood, and there are few available biomarkers. We utilized a novel proteomics approach to identify serum peptides and proteins associated with bone loss in 1967 older men who were randomly chosen from the Osteoporotic Fracture in Men Study (MrOS study) (age ≥ 65 yrs). Men had 2-3 measures of femoral neck BMD over an average follow-up of 4.6 years. Change in BMD was estimated and then categorized into three groups: maintained BMD (n=453), expected loss (n=1185) and accelerated loss (n=237). A liquid chromatography–ion mobility separation-mass spectrometry (LC-IMS-MS) proteomics platform was used to identify and quantify peptides from serum proteins. The whole cohort was randomly divided into discovery (N= 960) and validation (N= 915) sub-cohorts. Linear regression models and a random forest approach were used to discover differentially abundant individual peptides and a proteomic signature that distinguished individuals with accelerated bone loss from those who maintained BMD. Network analyses were performed using the MetaCore knowledgebase. We identified 12 peptides that were associated with BMD loss in both discovery (P< 0.1 FDR) and replication sub-cohorts (P<0.05). Those 12 peptides mapped to the following proteins: ALS, LYVE1, RNAS1, C2, ICOSL, C163A, C7, HEMO, CD14, CERU, CRAC1 and CD59. Meta-analysis of peptidesassociated with bone loss identified 6 additional proteins including GRP78, IGF-2, SHBG, ENPP2, IBP2 and IBP6. We also identified a proteomic signature that was predictive of BMD loss with a discriminative value similar to serum bone marker carboxy-terminal collagen crosslink peptide (CTX). Interestingly, combining the proteomic signature with CTX significantly improved the ability to discriminate men with accelerated loss. In summary, we have identified potential new biomarkers for bone loss that provide a more in depth understanding of its pathophysiology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Silver and gold doped hydroxyapatite nanocomposites for enhanced bone regeneration

In this work, we report the osteogenic potential of silver (Ag), gold (Au), or silver–gold doped hydroxyapatite nanoparticles (Ag-Au-HA) in zebrafish (ZF) jawbone regeneration (JBR) model. The hydroxyapatite (HA, Ca 10 (PO 4 ) 6 (OH) 2 ), Ag-HA, Au-HA, and Ag-Au-HA nanomaterials were synthesized by the co-precipitation procedure. The surface structures of Ag-HA, Au-HA, HA, and Ag-Au-HA were analysed by scanning electron microscopy, transmission-electron microscopy (TEM), x-ray diffraction, Fourier transform infrared (FTIR), UV–vis, energy dispersive x-ray spectroscopy (EDS), elemental mapping, and laser fluorescent spectroscopy. The TEM and EDS analysis confirmed that the Ag and Au are associated with the surface of HA nanoparticle. The chemical structure of HA, Ag-HA, Au-HA, and Ag-Au-HA nanoparticles was validated by FTIR and EDS analysis. We observed that Ag and Au are associated with HA nanoparticles by electrostatic, wander wall, and electrostatic and H-bonding interaction. The effect of Ag-HA, Au-HA, and Ag-Au-HA nanoparticles on bone regeneration was confirmed by ZF JBR model. The significant growth of ZF bone regeneration was observed in Ag-Au-HA nanoparticles as compared with HA, Ag-HA, and Au-HA nanoparticles. In conclusion, these results indicating a therapeutic potential of Ag-Au-HA compositions suggest these nanomaterials would be excellent for bone regeneration and fracture healing.

36 MATERIALS SCIENCE↗
NASA NTRS1999

The Effect of Spaceflight on Bone Cell Cultures

Understanding the response of bone to mechanical loading (unloading) is extremely important in defining the means of adaptation of the body to a variety of environmental conditions such as during heightened physical activity or in extended explorations of space or the sea floor. The mechanisms of the adaptive response of bone are not well defined, but undoubtedly they involve changes occurring at the cellular level of bone structure. This proposal has intended to examine the hypothesis that the loading (unloading) response of bone is mediated by specific cells through modifications of their activity cytoskeletal elements, and/or elaboration of their extracellular matrices. For this purpose, this laboratory has utilized the results of a number of previous studies defining molecular biological, biochemical, morphological, and ultrastructural events of the reproducible mineralization of a primary bone cell (osteoblast) culture system under normal loading (1G gravity level). These data and the culture system then were examined following the use of the cultures in two NASA shuttle flights, STS-59 and STS-63. The cells collected from each of the flights were compared to respective synchronous ground (1G) control cells examined as the flight samples were simultaneously analyzed and to other control cells maintained at 1G until the time of shuttle launch, at which point they were terminated and studied (defined as basal cells). Each of the cell cultures was assayed in terms of metabolic markers- gene expression; synthesis and secretion of collagen and non-collagenous proteins, including certain cytoskeletal components; assembly of collagen into macrostructural arrays- formation of mineral; and interaction of collagen and mineral crystals during calcification of the cultures. The work has utilized a combination of biochemical techniques (radiolabeling, electrophoresis, fluorography, Western and Northern Blotting, and light microscopic immunofluorescence) and structural methods (conventional and high voltage electron microscopy, inununocytochemistry, stereomicroscopy, and 3D image reconstruction). The studies have provided new knowledge of aspects of bone cell development and structural regulation, extracellular matrix assembly, and mineralization during spaceflight and under normal gravity. The information has contributed to insights into the means in general by which cells respond and adapt to different conditions of gravity (loading). The data may as well have suggested an underlying basis for the observed loss of bone by vertebrates, including man, in microgravity; and these scientific results may have implications for understanding bone loss following fracture healing and extended periods of inactivity such as during long-term bedrest.

Landis, William J.↗
NASA NTRS2014

Biomechanics of the Treadmill Locomotion on the International Space Station

Exercise prescriptions completed by International Space Station (ISS) crewmembers are typically based upon evidence obtained during ground-based investigations, with the assumption that the results of long-term training in weightlessness will be similar to that attained in normal gravity. Coupled with this supposition are the assumptions that exercise motions and external loading are also similar between gravitational environments. Normal control of locomotion is dependent upon learning patterns of muscular activation and requires continual monitoring of internal and external sensory input [1]. Internal sensory input includes signals that may be dependent on or independent of gravity. Bernstein hypothesized that movement strategy planning and execution must include the consideration of segmental weights and inertia [2]. Studies of arm movements in microgravity showed that individuals tend to make errors but that compensation strategies result in adaptations, suggesting that control mechanisms must include peripheral information [3-5]. To date, however, there have been no studies examining a gross motor activity such as running in weightlessness other than using microgravity analogs [6-8]. The objective of this evaluation was to collect biomechanical data from crewmembers during treadmill exercise before and during flight. The goal was to determine locomotive biomechanics similarities and differences between normal and weightless environments. The data will be used to optimize future exercise prescriptions. This project addresses the Critical Path Roadmap risks 1 (Accelerated Bone Loss and Fracture Risk) and 11 (Reduced Muscle Mass, Strength, and Endurance). Data were collected from 7 crewmembers before flight and during their ISS missions. Before launch, crewmembers performed a single data collection session at the NASA Johnson Space Center. Three-dimensional motion capture data were collected for 30 s at speeds ranging from 1.5 to 9.5 mph in 0.5 mph increments with a 12-camera system. During flight, each crewmember completed up to 6 data collection sessions spread across their missions, performing their normal exercise prescription for the test day, resulting in varying data collection protocols between sessions. Motion data were collected by a single HD video camera positioned to view the crewmembers' left side, and tape markers were placed on their feet, legs, and neck on specific landmarks. Before data collection, the crewmembers calibrated the video camera. Video data were collected during the entire exercise session at 30 Hz. Kinematic data were used to determine left leg hip, knee, and ankle range of motion and contact time, flight time, and stride time for each stride. 129 trials in weightlessness were analyzed. Mean time-normalized strides were found for each trial, and cross-correlation procedures were used to examine the strength and direction of relationships between segment movement pattern timing in each gravitational condition. Cross-correlation analyses between gravitational conditions revealed highly consistent movement patterns at each joint. Peak correlation coefficients occurred at 0% phase, indicating there were no lags in movement timing. Joint ranges of motion were similar between gravitational conditions, with some slight differences between subjects. Motion patterns in weightlessness were highly consistent at a given speed with those occurring in 1G, indicating that despite differing sensory input, subjects maintain running kinematics. The data suggest that individuals are capable of compensating for loss of limb weight when creating movement strategies. These results have important implications for creating training programs for use in weightlessness as practitioners can have greater confidence in running motions transferring across gravitational environments. Furthermore, these results have implications for use by researchers investigating motor control mechanisms and investigating hypotheses related to movement strategies when using sensory input that is dependent upon gravity.

DeWitt, John↗
NASA NTRS2017

New Developments in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASA's life sciences research to perform long duration, rodent experiments on the International Space Station (ISS) to study effects of the space environment on the musculoskeletal and neurological systems of mice as model organisms of human health and disease, particularly in areas of muscle atrophy, bone loss, and fracture healing. To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research Project at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. The Rodent Research Habitat provides a living environment for animals on ISS according to standard animal welfare requirements, and daily health checks can be performed using the habitats camera system. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Following each flight, through the Biospecimen Sharing Program (BSP), numerous tissues and thousands of samples will be harvested, and distributed from the Space Life and Physical Sciences (SLPS) to Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases. Together, the hardware improvements (enrichment, telemetry sensors, cameras), new capabilities (live animal return), and experience that the Rodent Research team has gained working with principal investigator teams and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical research objectives.

Shirazi, Yasaman↗
NASA NTRS1995

Estimates of volumetric bone density from projectional measurements improve the discriminatory capability of dual X-ray absorptiometry

To determine whether estimates of volumetric bone density from projectional scans of the lumbar spine have weaker associations with height and weight and stronger associations with prevalent vertebral fractures than standard projectional bone mineral density (BMD) and bone mineral content (BMC), we obtained posteroanterior (PA) dual X-ray absorptiometry (DXA), lateral supine DXA (Hologic QDR 2000), and quantitative computed tomography (QCT, GE 9800 scanner) in 260 postmenopausal women enrolled in two trials of treatment for osteoporosis. In 223 women, all vertebral levels, i.e., L2-L4 in the DXA scan and L1-L3 in the QCT scan, could be evaluated. Fifty-five women were diagnosed as having at least one mild fracture (age 67.9 +/- 6.5 years) and 168 women did not have any fractures (age 62.3 +/- 6.9 years). We derived three estimates of "volumetric bone density" from PA DXA (BMAD, BMAD*, and BMD*) and three from paired PA and lateral DXA (WA BMD, WA BMDHol, and eVBMD). While PA BMC and PA BMD were significantly correlated with height (r = 0.49 and r = 0.28) or weight (r = 0.38 and r = 0.37), QCT and the volumetric bone density estimates from paired PA and lateral scans were not (r = -0.083 to r = 0.050). BMAD, BMAD*, and BMD* correlated with weight but not height. The associations with vertebral fracture were stronger for QCT (odds ratio [QR] = 3.17; 95% confidence interval [CI] = 1.90-5.27), eVBMD (OR = 2.87; CI 1.80-4.57), WA BMDHol (OR = 2.86; CI 1.80-4.55) and WA-BMD (OR = 2.77; CI 1.75-4.39) than for BMAD*/BMD* (OR = 2.03; CI 1.32-3.12), BMAD (OR = 1.68; CI 1.14-2.48), lateral BMD (OR = 1.88; CI 1.28-2.77), standard PA BMD (OR = 1.47; CI 1.02-2.13) or PA BMC (OR = 1.22; CI 0.86-1.74). The areas under the receiver operating characteristic (ROC) curves for QCT and all estimates of volumetric BMD were significantly higher compared with standard PA BMD and PA BMC. We conclude that, like QCT, estimates of volumetric bone density from paired PA and lateral scans are unaffected by height and weight and are more strongly associated with vertebral fracture than standard PA BMD or BMC, or estimates of volumetric density that are solely based on PA DXA scans.

Non-NASA Center↗
DOE OSTI2021

Glucocorticoids suppressed osteoblast differentiation by decreasing Sema3A expression via the PIK3/Akt pathway

Highlights: • Dex decreased Sema3A expression by suppressing the PI3K/Akt pathway. • Sema3A reversed Dex-induced suppression of osteoblast differentiation. • Sema3A reversed the Dex-mediated reduced transcriptional activity of β-catenin. Glucocorticoids(GCs) are extensively used to treat inflammatory and autoimmune diseases. Excessive prolonged exposure to glucocorticoids is associated with an increased risk of osteoporosis. The inhibition of osteoblast differentiation by GCs is suggested as a major cause for GCs-induced osteoporosis (GIO). However, the precise mechanism underlying the role of GCs in osteoblasts differentiation is not fully elucidated. Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, enhances bone formation and promotes fracture healing, which is known to increase osteoblastic differentiation and stimulate osteogenesis in bone metabolism. Here, the present study explored the effect of Sema3A in osteoblast differentiation using dexamethasone (Dex) treatment of bone marrow stromal cells (BMSCs). Dex treatment decreased Sema3A expression in BMSCs in a dose-dependent manner. Moreover, Dex stimulation suppressed the differentiation of osteoblasts by reducing alkaline phosphatase (ALP) activity, osteoblastic marker genes expression and mineralization, but all of these effects were ameliorated by exogenous recombinant Sema3A administration. Furthermore, exogenous Sema3A administration reversed the Dex-mediated decrease in nuclear accumulation of β-catenin and β-catenin activity in BMSCs. Meanwhile, Dex was capable of simultaneously suppressing the phosphorylation of protein kinase B(Akt) and the expression level of Sema3A in BMSCs. These changes were significantly abolished by the PI3K/Akt agonist. These results suggest that Dex inhibits osteoblast differentiation by suppressing Sema3A expression via the PI3K/Akt pathway. These data provide new insights into the molecular mechanisms of Dex-induced osteoblast differentiation inhibition.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1999

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Halloran, B.↗
DOE OSTI2017

Upconverting Nanoparticles as Optical Sensors of Nano- to Micro-Newton Forces

Mechanical forces affect a myriad of processes, from bone growth to material fracture to touch-responsive robotics. While nano- to micro-Newton forces are prevalent at the microscopic scale, few methods have the nanoscopic size and signal stability to measure them in vivo or in situ. Here, we develop an optical force-sensing platform based on sub-25 nm NaYF 4 nanoparticles (NPs) doped with Yb 3+ , Er 3+ , and Mn 2+ . The lanthanides Yb 3+ and Er 3+ enable both photoluminescence and upconversion, while the energetically coupled d-metal Mn 2+ adds force tunability through its crystal field sensitivity. IN using a diamond anvil cell to exert up to 3.5 GPa pressure or ~10 μN force per particle, we track stress-induced spectral responses. The red (660 nm) to green (520, 540 nm) emission ratio varies linearly with pressure, yielding an observed color change from orange to red for α-NaYF 4 and from yellow–green to green for d-metal optimized β-NaYF 4 when illuminated in the near infrared. We record consistent readouts over multiple pressure cycles and hours of illumination. With the nanoscopic size, a dynamic range of 100 nN to 10 μN, and photostability, these nanoparticles lay the foundation for visualizing dynamic mechanical processes, such as stress propagation in materials and force signaling in organisms.

36 MATERIALS SCIENCE↗
NASA NTRS2019

Ionizing Radiation from Ex Vivo Sterilization Diminishes Fatigue but Not Static Murine Vertebral Body Mechanics

For a variety of medical and scientific reasons, human bones can be exposed to ionizing radiation. At relatively high doses (30,000±5,000 Gy), ex vivo ionizing radiation is commonly used to sterilize bone allografts. However, ionizing radiation in these applications has been shown to increase risk of fracture clinically and decrease bone quality. Previously, we observed a significant decrease in compressive static strength and fatigue life of ex vivo whole bones exposed to x-ray radiation at 17,000 Gy and above; no changes in compressive mechanical properties were observed for radiation doses of 1,000 Gy and below. The gap in doses between no mechanical change (1,000 Gy) and significant mechanical degradation (17,000 Gy) is large, and it is unclear at what dose mechanical integrity begins to diminish in whole bones, and if its effects differ in response to static versus cyclic mechanical loading. This is a major clinical concern, as trabecular and cortical bone allografts are commonly used in structural, load-bearing applications. To gain insight into the effect of ionizing radiation from 1,000-17,000 Gy, we conducted an ex vivo radiation study on the static and fatigue mechanical properties of the vertebral whole bone. Our objectives were to: (1) quantify the effect of exposure to ex vivo ionizing radiation on the mechanical integrity (compressive static and fatigue) of whole bones; and (2) evaluate, if there are observed differences in mechanics, if they differ in magnitude for static versus cyclic properties. The results of this study will give insight into the need for changes in protocols for bone allograft radiation sterilization procedures.

bone mechanics↗